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To investigate the predictors of annual treatment frequency in the second year of pro re nata (PRN) intravitreal ranibizumab (IVR) injections for diabetic macular edema (DME).A retrospective study.We reviewed 65 eyes of 60 patients with center-involved DME who received PRN IVR injections after 3 monthly loading doses. The central subfield thickness (CST) and qualitative findings were assessed on the spectral domain optical coherence tomography (SD-OCT) images. We then investigated whether the parameters at the baseline or at the 12-month visit were associated with treatment frequency in the second year.The number of ranibizumab injections decreased from 6 (4-8) during the first year to 2 (0-3) during the second year (P.001). The injection numbers during the first year (ρ = 0.259, P = .037) but not during the second year (ρ = 0.152, P = .226) were modestly related to the logarithm of the minimum angle of resolution (logMAR) improvement at 24 months. Multivariate analyses revealed that the CST (β = 0.336, P = .005) and hyperreflective walls in the foveal cystoid spaces (β = 0.273, P = .020) at baseline were associated with the number of IVR injections during the second year. The treatment frequency during the second year was also related to the CST (β = 0.266, P = .012), hyperreflective walls (β = 0.394, P = .002), and cumulative doses of ranibizumab injections (β = 0.294, P = .006) at the 12-month visit.The cumulative doses of ranibizumab injections, CST, and hyperreflective walls in the foveal cystoid spaces at the 12-month visit are designated predictors of the treatment frequency of ranibizumab injections during the second year in DME.

[Purpose] To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. [Design] Prospective, cross-sectional, observational study. [Participants] One hundred and forty-four eyes of 114 patients with diabetes. [Methods] Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. [Main Outcome Measures] The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. [Results] The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. [Conclusions] The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. [Financial Disclosure(s)] Proprietary or commercial disclosure may be found after the references.

To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population.Genome-wide association study (GWAS).Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses.We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants.Associations of genetic variants with AMD.A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P5.0 × 10Our findings imply shared genetic components conferring the risk of both AMD and CSC.Proprietary or commercial disclosure may be found after the references.

To evaluate the association between central serous chorioretinopathy (CSC) susceptibility genes and choroidal parameters in a large Japanese cohort.Retrospective cohort study.Of the 9850 individuals in the Nagahama study whose second visit was between 2013 and 2016, those with optical coherence tomography (OCT) images with enhanced depth imaging (EDI), axial length, and genome-wide single nucleotide polymorphism (SNP) genotyping data were included. We calculated subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), normalized choroidal intensity (NCI), and vertical asymmetry of choroidal thickness. Genome-wide quantitative trait locus (QTL) analyses were performed for each parameter. We screened for four CSC susceptibility SNPs: CFH rs800292, TNFRSF10A rs13278062, GATA5 rs6061548, and VIPR2 rs3793217. Whenever an SNP was not included in the genotyping data after quality control, its proxy SNP was selected.In total, 4586 participants were evaluated. CFH rs800292 was significantly associated with SFCT (P0.001) and CVI (P0.001). VIPR2 rs3793217 was significantly associated with SFCT (P0.001) but not with CVI. Whereas, TNFRSF10A rs13254617 and GATA5 rs6061548 were not significantly associated with SFCT or CVI. None of these SNPs was associated with NCICFH, VIPR2, TNFRSF10A, and GATA5 showed different association patterns with choroidal parameters. Although the mechanism of CSC pathogenesis by choroidal changes is not fully understood, this finding suggests that each gene may be involved in different mechanisms of CSC development. Our genetic study provides a basis for understanding the role of CSC susceptibility genes.

PurposeTo characterise the non-perfused areas (NPAs) in the superficial and deep capillary layers (sNPAs and dNPAs, respectively) in the posterior pole in proliferative diabetic retinopathy (PDR) on wide-field optical coherence tomography angiography (OCTA) images.MethodsWe retrospectively reviewed 104 eyes of 70 patients with PDR from whom wide-field swept source OCTA images were acquired. sNPAs and dNPAs were manually measured in each quadrant of the inner (1–3 mm diameter), intermediate (3–6 mm), and outer (6–10 mm) rings centred on the fovea. Two qualitative findings, that is,segmented NPAsandperiarteriolar NPAs, were also compared.ResultsThe dNPAs were greater than the sNPAs (pρ=0.341, p=0.026) and outer (ρ=0324, p=0.032) rings, whereas sNPAs exhibited no associations.Segmented NPAswere delineated more frequently in the superficial layer than in the deep layer (pPeriarteriolar NPAswere more frequent in the deep layer (pConclusionsThree-dimensional assessment of wide-field OCTA promotes a better understanding of the enigmatic disproportion of lamellar NPAs in the posterior pole in PDR.

Purpose To compare the characteristics of macular and extramacular white spots on wide-field swept-source optical coherence tomography angiography (SS-OCTA) and optical coherence tomography (OCT) images in diabetic retinopathy (DR). Methods We retrospectively reviewed 107 eyes of 64 patients with DR, of whom nominal 12 × 12 mm SS-OCTA images centered on the optic disc and ultrawide field photographs were acquired. White spots on fundus photographs corresponded to hyperreflective lesions in the superficial en-face OCT images, and the characteristics of these white spots were investigated. We compared such OCT findings with the vertical and horizontal extents of nonperfused areas (NPAs) on OCTA images. Results We observed 136 white spots and corresponding hyperreflective lesions in 49 eyes. The hyperreflective lesions in the extramacular areas had greater areas (P < 0.001) and more frequently spanned from the nerve fiber layer to the outer plexiform layer (P < 0.001), while those in the macula were superficial. All of macular hyperreflective lesions were accompanied with nerve fiber layer defects, whereas only 18 (15.4%) of 117 extramacular lesions had them (P < 0.001). Comparative studies showed that most extramacular hyperreflective lesions corresponded to the NPAs in the whole layers on OCTA images, compared to the lamellar NPAs of the superficial layer in most of the macular lesions (P < 0.001). The NPAs extended to the peripheral side more frequently in the extramacular hyperreflective lesions compared with macular lesions (P < 0.001). Conclusions This study proposed that most of the extramacular white spots may be discriminated from macular spots with respect to diabetic NPAs on OCTA images.